Reconsolidation of Emotional Memory in Humans

描述(由申请人提供)：详细的动物研究提供了强有力的证据，表明每次提取后情绪记忆都会重新巩固，蛋白质合成抑制剂或β-肾上腺素能拮抗剂可以削弱这一过程(例如，Nadar等人，2000；Debiec和Ledoux，2004)。与记忆一旦通过不稳定的形成状态到完全巩固就是稳定的概念相反，这一基本发现表明，可能存在损害旧的情感记忆的机会之窗，更重要的是，创伤记忆。然而，到目前为止，还没有证据表明人类存在这样的过程。目前提出的这项研究的目的是寻找人类情绪记忆重新巩固的证据，并阐明其潜在的大脑机制。我们的策略将是检查正常健康人类志愿者的再巩固，使用与动物相同的程序。这些程序旨在检测杏仁核和海马体这两个与焦虑和情绪障碍有关的大脑区域对重新巩固过程的具体贡献。具体地说，我们将试图通过检测β-肾上腺素能阻滞剂心得安对恐惧条件反射及其上下文调节的影响，为人类杏仁核和海马区依赖记忆的重新巩固提供第一个证据。有两个具体的目标：具体目标1：我们将使用线索恐惧条件反射范式，研究β-肾上腺素能受体阻断对人类杏仁核依赖记忆再巩固的影响；b)我们将研究β-肾上腺素能受体阻断对杏仁核依赖记忆再巩固的影响所引起的杏仁核依赖记忆再提取变化的神经机制。具体目标2：a)我们将使用情境介导的恐惧恢复范式，研究β-肾上腺素能受体阻断对人类海马区依赖记忆再巩固的影响；b)我们将研究由β-肾上腺素能受体阻断对再巩固的影响而导致的海马区依赖记忆再提取改变的神经机制。

DESCRIPTION (provided by applicant): Detailed animal studies provide strong evidence that emotional memories are reconsolidated each time after retrieval, and that protein synthesis inhibitors or beta-adrenergic antagonists can impair this process (e.g., Nadar et al., 2000; Debiec and Ledoux, 2004). In contrast to the notion that memories are stable once they have passed the labile state of formation to being fully consolidated, this basic finding suggests there might be a window of opportunity to impair old emotional memories, and more importantly, traumatic memories. However, to date, there is no evidence that such a process exists in humans. The aim of the current proposed research is to find evidence for reconsolidation of emotional memory in humans, and to elucidate its underlying brain mechanisms. Our strategy will be to examine reconsolidation in normal healthy human volunteers, using procedures that mirror those used in animals. These procedures will be aimed at detecting specific contributions of the amygdala and the hippocampus, two brain regions implicated in anxiety and emotional disorders, to reconsolidation processes. Specifically, we would attempt to provide the first evidence for reconsolidation of human amygdala and hippocampal dependent memories by examining the effects of the beta-adrenergic blocker propranolol on fear conditioning and its contextual modulation. There are two specific aims: Specific Aim 1: a) We will examine the effects of beta-adrenergic receptor blockade on reconsolidation of amygdala-dependent memories in humans, using a cue fear-conditioning paradigm; b) We will investigate the neural mechanisms underlying alterations in re-retrieval of amygdala-dependent memories induced by beta-adrenergic blockade effects on reconsolidation. Specific Aim 2: a) We will examine the effects of beta-adrenergic receptor blockade on reconsolidation of hippocampal-dependent memories in humans, using a context-mediated fear reinstatement paradigm; b) We will investigate the neural mechanisms underlying alterations in re-retrieval of hippocampal-dependent memories induced by beta-adrenergic blockade effects on reconsolidation.